Chemical Classification Based on Purity

• Chemicals are classified based on purity.
• The purity classifications are commercial, pure, pharmaceutical, and analytical.
• Analytical reagent is also known as Anal R.

Commercial Chemical

• These chemicals possess the lowest level of purity.
• They are also known as industrial or technical chemicals.
• Commercial chemicals are generally the cheapest because they are prepared without precautions against contamination.

Pure Chemical

• They contain a very small amount of impurities.
• Containers should be labeled with both the quality and quantity of impurities present.
• Pure sulfuric acid contains 10 ppm lead, 1-2 ppm chloride, and 0.5 ppm arsenic.

Pharmaceutical Chemical

• Pharmaceutical chemicals are used for pharmaceutical preparations either internally or externally.
• Pharmaceutical chemicals must be chemically pure, free of toxic materials, and conform to pharmacopoeia requirements.

Analytical Chemical

• Analytical chemicals are the highest purity chemicals as they contain the lowest possible amount of impurities.
• They are also known as analytical reagents (Anal.R).
• Analytical reagents are the most expensive, and are used for preparing primary standard reagents and for research.

Sources of Impurities in Pharmaceutical Chemicals

• Impurities in pharmaceutical chemicals stem from raw materials used for pharmaceutical preparation can contain iron impurities.
• Copper salts prepared from copper pyrites contain iron impurities.
• Sodium chloride from seawater often includes magnesium and calcium salts.

Manufacturing Process Impurities

• Impurities can enter pharmaceutical products during manufacturing, such as from reagents.
• Hydrogen peroxide may contain trace barium from barium salts used to remove excess sulfate from sulfuric acid which is used with sodium peroxide to prepare hydrogen peroxide.
• Calcium carbonate can contain soluble alkali impurities from sodium carbonate when used with calcium chloride to prepare calcium carbonate.

Solvent Impurities

• Water, a common and cheap solvent, can introduce impurities if tap water is used.
• Hard water contains traces of calcium, magnesium, sodium, chloride, and carbonate, which can act as impurities.

Container Impurities

• Metallic containers can introduce metallic impurities.
• Glass containers may release alkalinity impurities.
• Plastic containers should be special types or stainless steel lined with natural glass, or made from thermo-stable acid and alkali-resistant plastic.

Atmosphere Impurities

• Atmospheric pollution increases contamination risk due to dust containing aluminum oxide, silica, and sulfur.
• Atmospheric vapor of carbon dioxide and water can affect chemicals if stored improperly.

Auto-Decomposition or Chemical Instability

• Hydrolysis, oxidation, or reduction during storage can create undesirable impurities.
• Chloroform oxidizes in air to form toxic phosgene; 1-2% ethanol is added to transform toxic phosgene into non-toxic diethyl carbonate.

Decomposition

• Chemical decomposition during manufacturing can occur from ionizing radiation or sterilization, leading to impurities that reduce potency or create toxic products.

Adulteration

• Adulteration, especially in expensive compounds, is a common impurity source.
• It poses a serious problem in the pharmaceutical industry when cheaper chemicals with faked ingredients are added.

Limit Tests Defined

• Limit tests are quantitative or semi-quantitative tests in official monographs of pharmacopoeias like BP and USP.
• They are designed to identify and control small quantities of impurities in pharmaceutical and chemical preparations.

Requirements for Limit Tests

• Tests should be specific (selective).
• Tests should be sensitive.
• Personal error should be controlled by using a comparison method or an applied quantitative method.

Types of Impurity Limit Tests

• General limit tests for non-specific impurities should be used
• Limits for metallic impurities
• Limits for non-metallic impurity
• Limits for acid radicals impurity
• Limit test for organic impurity.

Limit test for Metallic Impurity

• These tests are applied to metals that widespread due to atmospheric pollution and cause physiologically harmful impurities.
• These metals include arsenic, antimony, lead, cadmium, mercury, and iron.

Limit Tests for Metallic Impurities

• Test for heavy metals.
• Test for iron.
• Test for arsenic.
• Metallic Impurities - test for alkaline earths & related impurities.

Limit Test for Heavy Metals

• Heavy metals darken when exposed to sodium or hydrogen sulfide.
• The reaction with hydrogen sulfide involves mixing the test solution with freshly prepared sulfide.
• Color comparison is done directly in suitable comparison tubes.

Limit Test for Lead

• The principal way to test is by traces conversion of lead salts to lead sulphide.
• The conversion is done via sodium sulphide addition in a slightly alkaline buffer with ammonium acetate.
• Lead salts + sodium sulphide become, after ammonium acetate buffer, lead sulphide with a colloidal brown color.
• Use flat-bottomed comparison tubes of transparent glass of about 70 ml capacity and about 23 mm internal diameter known as Nessler tube.
• The brown color from colloidal lead sulphide in test solution is compared with a known amount of lead.

Determination Of Lead

• Lead can be detected directly by precipitation with sodium hydrogen sulfide (NaHS).
• A sample extraction can be done with chloroform, then measure the colored complex from Pb with dithizone, such as ferrous sulphate and Dextrose.
• Atomic absorption spectroscopy can be used to detect lead in Lactose and Bismuth milk.

Limit Test For Iron

• The test of iron is based on purple colour obtained from the reaction of iron and thioglycollic acid in a solution buffered with ammonium citrate.
• It demonstrates the content of iron does not exceed the standard color containing a known amount of iron (40 µg of iron).

Limit Test for Arsenic

• Arsenic is highly toxic.
• The Gutzeit test is based on yellow color production through the reaction of arsenic and mercuric bromide.
• The resulting stain should not be more intense than the standard (1 ml of arsenic standard solution "1 ppm As" diluted to 25 ml).

Limit Test For Magnesium Present In Calcium Carbonate

• Testing includes calcium chloride and gluconate, dil. H₂SO₄ addition to the sample, ppt resulted as sulphate salt.
• Alkali metal as calcium acetate is detected by atomic absorption.
• Aluminum is tested by its color reaction with 8-hydroquinoline, measured calorimetrically.

Limit Test for Non-Metallic Impurities

• Non metalic such as boron, free halogen and selenium.
• Boron tested by conversion to borate then determined colorimetrically-it causes unwanted skin reaction, toxic to nerves.

Limit test for Non-Metallic Impurities and Free Halogens

• Free halogen as iodine in iodipamide meglumine injection is examined using starch.
• Absorption iodine in iophendylate is detected by the absorption at 485 nm.

Limit test for Non-Metallic Impurities and Selenium

• Selenium is detected by destruction of an organic compound with nitric acid, which producing a selenious acid.
• Diaminobenzidine can treat resulting selenous acid which producing complex colors to measure

Limit Test for Acid Radical Impurities

• Acid radicals is identified through chloride and sulphate that results from the use of tap water in manufacturing.
• The test for chloride depends of the precipitation of the chloride with silver nitrate, the solution is then compared with an opalescent solution with known chloride.

Test for Sulphate Acid Radicals

• It depends upon soluble sulphate interaction with barium chloride in presence of HCL.
• The opalescent solution is compared to turbidity with sulphate ion amount.

Limit Test for Organic Matters Impurities

• The quantification of an impurity is performed by using a reference impurity solution.
• Solution containing a known amount of the impurity is used and then its expresses the real percentage of the impurity in the sample.

Additional Testing for Organic Matter Impurities

• These methods include high-performance liquid chromatography (HPLC).
• Other methods include mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectrometry.
• Modern software that is directly coupled is also effective at detecting trace levels of impurities.
• For volatile and thermally compounds, use gas chromatography along with various detection systems.
• Capillary electrophoresis and solid phase microextraction/GC-MS are also used.
• Multiple analytical systems are used to confirm organic impurities.